Suggest an unanticipated biological function of IRE1alpha in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton.

ovarian cancer--an aggressive malignancy that is refractory to standard treatments and current immunotherapies--induces endoplasmic reticulum stress and activates the IRE1alpha-XBP1 arm of the unfolded protein response in T cells to control their mitochondrial respiration and anti-tumour function

While PERK complexes shift to large complexes, ATF6alpha complexes are reduced to smaller complexes on endoplasmic reticulum (ER) stress. In contrast, IRE1alpha complexes were not significantly increased in size on ER stress, unless IRE1alpha is overexpressed.

This study provides the first demonstration of a dual role of IRE1 downstream signaling in cancer and opens a new therapeutic window to abrogate tumor progression.

IRE1alpha acts in a feed-forward loop during obesity-induced metabolic inflammation to promote hepatocellular carcinoma development through STAT3-mediated hepatocyte proliferation

necrotic cell lysates induce JNK/SAPK signaling, the IRE1alpha branch of the unfolded protein response (UPR), the MAPK/ERK1/2, and the mTOR signaling pathways and results in an enhanced proliferation of the vital surrounding cells.

Here, the authors show that similar to yeast, human IRE1alpha's endoplasmic reticulum-lumenal domain (hIRE1alpha LD) binds peptides with a characteristic amino acid bias. Peptides and unfolded proteins bind to hIRE1alpha LD's MHC-like groove and induce allosteric changes that lead to its oligomerization.

Three branches of the Unfolded Protein Response (UPR) have been described, including the activation of the inositol-requiring enzyme 1 (IRE1), the pancreatic ER kinase (PKR)-like ER kinase (PERK), and the activating transcription factor 6 (ATF6).

IRE1alpha is expressed at lower levels in higher-grade gliomas, suggesting greater antitumor efficacy of the oncolytic virus M1. Taken together, these findings illustrate a defensive mechanism of glioma cells against the oncolytic virus M1 and identify possible approaches to enhance the oncolytic viral protein accumulation and the subsequent lysis of tumor cells.

Systematic mutation of the AREs (ARE1-3) in the LDLR 3'UTR and expression of each mutant coupled to a luciferase reporter in Huh7 cells demonstrated that ARE1 is required for rapid LDLR mRNA decay and 5-AzaC-induced mRNA stabilization via the IRE1alpha-EGFR-ERK1/2 signaling cascade.

Present study demonstrates that fine-tuning of the expression of proliferation related transcription factor genes depends upon glucose and glutamine deprivation in IRE1-dependent manner and possibly contributes to slower tumor growth after inhibition of IRE1.

The authors found that estrogen signals through estrogen receptor alpha (ERalpha) expressed in hematopoietic cells to activate the protective Ire1alpha-Xbp1 branch of the unfolded protein response.

These observations were validated in vivo in the liver of IRE1a conditional knockout mice, revealing broad implications for cellular metabolism. Our results support an alternative function of IRE1alphaain orchestrating the communication between the endoplasmic reticulum and mitochondria to sustain bioenergetics

IRE1 undergoes phosphorylation at S729.

These findings provide a novel mechanism by which XBP1s stimulate insulin sensitivity in adipocytes through fibroblast growth factor 21 induction and PPARgamma activation.

Suggest an unanticipated biological function of IRE1alpha in cell migration, whereby filamin A operates as an interphase between the UPR and the actin cytoskeleton.

IRE1alpha-XBP1 pathway plays an important role in the efficient folding of proinsulin and transcriptional induction of the five PDI family proteins, which are critical for correct disulfide bond formation of proinsulin, in pancreatic beta cells.

IRE1alpha acts in a feed-forward loop during obesity-induced metabolic inflammation to promote hepatocellular carcinoma development through STAT3-mediated hepatocyte proliferation

Targeting IRE1alpha-dependent NLRP3 inflammasome signaling with pharmacological agents or by BI-1 may represent a tangible therapeutic strategy for nonalcoholic steatohepatitis

IRE1alpha has a critical role in colonic tumorigenesis and IRE1alpha targeting might be a strategy for treatment of colon cancers.

Study provided the first link between energy homeostasis, lipid metabolism and pro-opiomelanocortin (POMC) neuronal IRE1alpha function. The effects of POMC IRE1alpha knockout were mediated via increased thermogenesis, possibly caused by the increased alpha-MSH production in the hypothalamus. These results demonstrate that IRE1alpha in POMC neurons plays a critical role in the regulation of obesity and obesity-related m...

Fortilin directly interacts with the cytoplasmic domain of IRE1alpha, inhibits both kinase and endoribonuclease (RNase) activities of this stress sensor, and protects cells against apoptotic cell death at both cellular and whole animal levels.

ERN1 Antigen-Profil

Beschreibung des Gens

The protein encoded by this gene is the ER to nucleus signalling 1 protein, a human homologue of the yeast Ire1 gene product. This protein possesses intrinsic kinase activity and an endoribonuclease activity and it is important in altering gene expression as a response to endoplasmic reticulum-based stress signals.